Pregnancy after liver and other transplantation

Ignazio R. Marino, Lucio Mandalà, and Augusto Lauro

Introduction and Historic Notes

Since the first human liver transplant performed in 1963 by Thomas Starzl (University of Colorado) [1], many advances in surgical techniques and immunosuppressive therapy have helped to increase the numbers of women who undergo allogenic organ transplantation each year. In 1978, Walcott [2] documented the first known pregnancy in a liver transplant recipient, which resulted in a successful delivery with both mother and infant in excellent health. Many times, a transplanted organ normalizes a woman’s hormonal imbalance and restores fertility, thus offering the prospect of pregnancy and providing many women with end-stage organ disease a chance to conceive and bear children. As a result, among liver transplant recipients, a higher survival rate and a return to a good quality of life have been achieved. In 1991, the National Transplantation Pregnancy Registry (NTPR) was established at Thomas Jefferson University in Philadelphia, Pennsylvania, to analyze pregnancy outcomes in solid-organ transplant recipients [3].

Definition/Symptoms and Signs of ESLD

Liver transplantation (LTx): treatment of choice for all nonneoplastic end-stage liver diseases and for selected patients with nonresectable hepatic malignancies. End-stage liver disease (ESLD): any hepatic disease that jeopardizes the survival or that seriously modifies the quality of life of the patient and for which the transplant is the only therapy because no other medical or surgical treatment exists that is able to provide a reasonable chance of recovery. Before undergoing LTx, some patients remain in quite good clinical condition. There may be individual variations in terms of hospital care requirements. As the liver disease progresses, symptoms such as encephalopathy, weakness, and lethargy become more frequent. Intractable ascites, GI bleeding, peripheral edema, anorexia, jaundice, pruritus and cholestasis, peritonitis, and pneumonia may also develop. Often the patient is severely malnourished.

Indications

Although chronic hepatitis C infection (HCV) represents the leading indication for LTx in the United States, autoimmune hepatitis is probably the most frequent reason for transplantation among young female recipients who may become pregnant after transplant [4].

Epidemiology

Approximately one third of all patients who have undergone LTx are women, and about 75% of female recipients are of reproductive age [4]. The incidence indicates that more than 14,000 women of reproductive age are living in the United States after liver transplantation (LTx), and another 500 undergo LTx each year [5].

Pathophysiology

Women with decompensated liver disease commonly have menstrual dysfunction: Infertility is common in women with ESLD because of hypothalamic–pituitary–gonadal dysfunction, which decreased ovulation [6,7] and affects up to 50% of these patients. In fact, menstrual abnormalities may be the first signs of liver disease in females with chronic liver disease. In cirrhotic state, hypothalamic–pituitary dysfunction is associated with an inadequate response to the gonadotropinreleasing hormone agonists and clomiphene citrates as well as diminished gonadotrophin release relative to the reduced levels of circulating sex steroids [8]. Furthermore, serum levels of estradiol and testosterone are increased in patients with porto-systemic shunts. Thus pregnancy in decompensated cirrhosis is very uncommon. A successful transplant almost uniformly leads to a prompt return to normal menstrual cycles and to reproductive functions because of the recovery of the gonadotrophic function [8–11]. This is an important component of the restoration of normality of life for patients of childbearing age, and it is evidenced by the increasing number of post-transplantation pregnancies reported worldwide [12–24].

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